ovarian cancer
Conditions
Interventions
- Group A Chemotherapy alone followed by observation
- Groep B Chemotherapy alone followed by maintenance phase with Avelumab
- Groep C Chemotherapy + Avelumab followed by maintenance phase with Avelu
Avelumab
Ovarian Cancer
Sponsors
Pfizer
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed Stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer (according to AJCC/UICC TNM and International Federation of Gynecology and Obstetrics (FIGO) Staging System 2014 edition), including malignant mixed Müllerian tumors with high grade serous component. 2. Patients must be candidates for platinum-based chemotherapy and previously untreated. 3. Patients must have completed a surgical debulking procedure, or be candidates for neoadjuvant chemotherapy. a. For patients enrolling after debulking surgery, the following conditions must be met: * The minimum surgery required is an abdominal surgery with an attempt at cytoreduction providing tissue for histologic evaluation and establishing and documenting the primary site and stage * Patient must be randomized at a maximum of 8 weeks after surgery. b. For patients who are candidates for neoadjuvant chemotherapy, the following conditions must be met: * A core tissue (not fine needle aspiration) biopsy is required. The tissue must be consistent with a tumor of Müllerian origin. * Stage IIIC*IV documented via imaging or surgery (without attempt at cytoreduction) * Serum CA125/ CEA ratio > 25. If the serum CA125/CEA ratio is
Exclusion criteria
Exclusion criteria: 1. Non-epithelial tumors, or ovarian tumors with low malignant potential (ie, borderline tumors). 2. Mucinous tumors. 3. Patients for whom, in the opinion of the Investigator, there is clinical benefit to administer bevacizumab as a first-line treatment and for whom bevacizumab is approved and available in this setting. 4. Cancer for which intraperitoneal cytotoxic chemotherapy is planned. 5. Prior systemic anti-cancer treatment for EOC, FTC, or PPC. 6. Prior immunotherapy with IL-2, IFN-*, or anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T lymphocyte associated antigen 4 (anti-CTLA-4) antibody (including ipilimumab), or any other antibody or drug specifically targeting T cell costimulation or immune checkpoint pathways. 7. Major surgery (other than debulking surgery) for any reason within 4 weeks prior to randomization and/or incomplete recovery from surgery. 8. Known brain, leptomeningeal, or spinal cord metastases. 9. Current or prior use of immunosuppressive medication within 7 days prior to randomization, except the following: intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection); systemic corticosteroids at physiologic doses *10 mg/day of prednisone or equivalent; steroids as premedication for hypersensitivity reactions [eg, computed tomography (CT) scan premedication]. 10. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agents except patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroidism not requiring immunosuppressive treatment. 11. Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, deep vein thrombosis or symptomatic pulmonary embolism. 12. Active and clinically significant bacterial, fungal or viral infection, any positive tests for hepatitis B (HBV), hepatitis C (HCV) indicating acute or chronic infection(positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive), known history of a positive human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS) related illness. 13. Administration of a live vaccine within 30 days prior to study entry. 14. Known severe hypersensitivity reactions to monoclonal antibodies, carboplatin, or paclitaxel or other platinum-containing compounds (NCI CTCAE v4.03 Grade *3). 15. Persisting NCI CTCAE v4.03 Grade >1 toxicity related to prior therapy. 16. Previous malignant disease other than the target malignancy to be investigated in this trial within the last 5 years with the exception of adequately treated basal or squamous cell carcinoma of the skin, cervical carcinoma in situ, lobular carcinoma in situ (LCIS), or ductal carcinoma in situ (DCIS). 17. Patients who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees directly involved in the conduct of the study. 18. Participation in other clinical studies involving investigational drug(s) within 4 weeks prior to study randomization and/or during study participation. 19. Other severe/severe acute or chronic medical, including colitis, inflammatory bowel disease, and pneumo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint of the study is Progression-Free Survival (PFS). | — |
Secondary
| Measure | Time frame |
|---|---|
| Other efficacy endpoints include overall survival (OS), objective reponse (OR), and duration of response (DR). This study will also include additional efficacy endpoints, PFS2, pathological complete response (pCR) and PFS by GCIG criteria, as defined below. PFS2: PFS2 is defined by the European Medicines Agency (EMA) guidance (EMA, 2012) as the time from randomization to second objective disease progression, or death from any cause, whichever occurs first. However, continued collection of scans and RECIST assessment after discontinuation from the study is logistically challenging. In the absence of reliable tumor assessments, the end of next line treatment has been proposed as a surrogate (EMA, 2012). In ovarian cancer patients, however, first subsequent treatment is anticipated to mostly consist of a fixed/ planned number of cycles and end of treatment therefore might not reflect disease progression. There is limited experience with PFS2 in ovarian cancer, although it has been proposed as an endpoint to explore in future studies. In this protocol, PFS2 is defined as time from randomization to the start of second subsequent treatment after first documentation of objective progression of disease, or death from any cause. In the setting of ovarian cancer, start of second subsequent therapy was deemed to be the most reliable and unequivocal evidence of second progression. pCR: Compared to breast cancer, there is relatively little experience with using the rate of pCR as a surrogate endpoint in ovarian cancer. There are also challenges in standardization of pCR assessment, since unlike breast cancer it is difficult to accurately sample the entire tumor bed. A recent study by Bohm et al, 2015,68 has tested and validated the prognostic significance of a 3 tier scoring system for grading pathological response to neoadjuvant therapy in patients with high grade pelvic serous carcinoma. The study included 60 patients in the test cohort and 71 patien | — |
Countries
Bulgaria, Canada, Croatia, Estonia, Germany, Hong Kong, Hungary, Ireland, Italy, Japan, Korea (the Republic of), Latvia, Mexico, Netherlands, Poland, Romania, Russian Federation, Singapore, Slovakia, Switzerland, Taiwan (Province of China), Turkey, Ukraine, United Kingdom, United States of America
Outcome results
None listed